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26.
  • Haldrup, Kristoffer, et al. (author)
  • Ultrafast X-Ray Scattering Measurements of Coherent Structural Dynamics on the Ground-State Potential Energy Surface of a Diplatinum Molecule
  • 2019
  • In: Physical Review Letters. - 0031-9007. ; 122:6
  • Journal article (peer-reviewed)abstract
    • We report x-ray free electron laser experiments addressing ground-state structural dynamics of the diplatinum anion Pt2POP4 following photoexcitation. The structural dynamics are tracked with <100 fs time resolution by x-ray scattering, utilizing the anisotropic component to suppress contributions from the bulk solvent. The x-ray data exhibit a strong oscillatory component with period 0.28 ps and decay time 2.2 ps, and structural analysis of the difference signal directly shows this as arising from ground-state dynamics along the PtPt coordinate. These results are compared with multiscale Born-Oppenheimer molecular dynamics simulations and demonstrate how off-resonance excitation can be used to prepare a vibrationally cold excited-state population complemented by a structure-dependent depletion of the ground-state population which subsequently evolves in time, allowing direct tracking of ground-state structural dynamics.
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27.
  • Herchenhan, Andreas, et al. (author)
  • Early Growth Response Genes Increases Rapidly After Mechanical Overloading and Unloading in Tendon Constructs
  • 2020
  • In: Journal of Orthopaedic Research. - : WILEY. - 0736-0266 .- 1554-527X. ; 38:1, s. 173-181
  • Journal article (peer-reviewed)abstract
    • Tendon cells exist in a dense extracellular matrix and mechanical loading is important for the strength development of this matrix. We therefore use a three-dimensional (3D) culture system for tendon formation in vitro. The objectives of this study were to elucidate the temporal expression of tendon-related genes during the formation of artificial tendons in vitro and to investigate if early growth response-1 (EGR1), EGR2, FOS, and cyclooxygenase-1 and -2 (PTGS1 and PTGS2) are sensitive to mechanical loading. First, we studied messenger RNA (mRNA) levels of several tendon-related genes during formation of tendon constructs. Second, we studied the mRNA levels of, for example, EGR1 and EGR2 after different degrees of loading; dynamic physiologic-range loading (2.5% strain), dynamic overloading (approximately 10% strain), or tension release. The gene expression for tendon-related genes (i.e., EGR2, MKX, TNMD, COL3A1) increased with time after seeding into this 3D model. EGR1, EGR2, FOS, PTGS1, and PTGS2 did not respond to physiologic-range loading. But overloading (and tension release) lead to elevated levels of EGR1 and EGR2 (p amp;lt;= 0.006). FOS and PTGS2 were increased after overloading (both p amp;lt; 0.007) but not after tension release (p = 0.06 and 0.08). In conclusion, the expression of tendon-related genes increases during the formation of artificial tendons in vitro, including EGR2. Furthermore, the gene expression of EGR1 and EGR2 in human tendon cells appear to be sensitive to overloading and unloading but did not respond to the single episode of physiologic-range loading. These findings could be helpful for the understanding of tendon tensional homeostasis. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
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28.
  • Hoeffner, Rikke, et al. (author)
  • Muscle fascicle and sarcomere adaptation in response to Achilles tendon elongation in an animal model
  • 2023
  • In: Journal of applied physiology. - : AMER PHYSIOLOGICAL SOC. - 8750-7587 .- 1522-1601. ; 135:2, s. 326-333
  • Journal article (peer-reviewed)abstract
    • Permanent loss of muscle function seen after an Achilles tendon rupture may partly be explained by tendon elongation and accompanying shortening of the muscle. Muscle fascicle length shortens, serial sarcomere number is reduced, and the sarcomere length is unchanged after Achilles tendon transection (ATT), and these changes are mitigated with suturing. The method involved in this study was a controlled laboratory study. Two groups of rats underwent ATT on one side with a contralateral control (CTRL): A) ATT with 3 mm removal of the Achilles tendon and no suturing (substantial tendon elongation), and B) ATT with suture repair (minimal tendon elongation). The operated limb was immobilized for 2 wk to reduce load. Four weeks after surgery the rats were euthanized, and hindlimbs were analyzed for tendon length, gastrocnemius medialis (GM) muscle mass, length, fascicle length, sarcomere number and length. No differences were observed between the groups, and in both groups the Achilles tendon length was longer (15.2%, P < 0.001), GM muscle mass was smaller (17.5%, P < 0.001), and muscle length was shorter (8.2%, P < 0.001) on the ATT compared with CTRL side. GM fascicle length was shorter (11.2%, P < 0.001), and sarcomere number was lower (13.8%, P < 0.001) on the ATT side in all regions. Sarcomere length was greater in the proximal (5.8%, P < 0.001) and mid (4.2%, P 1/4 0.003), but not distal region on the ATT side. In this animal model, regardless of suturing, ATT resulted in tendon elongation, loss of muscle mass and length, and reduced serial sarcomere number, which resulted in an "overshoot" lengthening of the sarcomeres.
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29.
  • Hoff Rudhult, Maria (author)
  • SIDA VID SIDA? : Svenska företag i biståndsverksamheten, 1946–2013
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • This thesis studies how the way private businesses were viewed came to affect their participation, and thus role, in Swedish development aid activities in the 1946-2013 period. The role is here viewed in terms of the relationship between “the public” and “the private”. The relationship between public and private activities, as well as the distinction between them, is mutable, and needs to be understood within the framework of a specific context. This, in turn, means that these relationships between the state, in the form of public activity, and the businesses, in the form of private activity, constitute the more comprehensive research problem of the thesis. The analytical strategy of the thesis is based on a discourse theoretical approach, discursive institutionalism, to study how development aid, based on the ideal of “solidarity”, was formulated, established and upheld as an area of policy, focusing especially on the role that was concurrently created for Swedish private businesses. The application of a genealogical approach in the reading of political texts as well as archival material, reports and evaluations, makes visible how the businesses have been part of the Swedish developmental aid activities during practically the entirety of the time period studied, and that this has not been openly accounted for in the public political material. The study shows that upholding the ideal of the “solidarity-based” politics regarding development aid was enabled by applying different logics of action to different parts of the development aid activity. This is made clear by the political ability to involve businesses in development aid activities without having to expressly renounce the position of solidarity. The result of the thesis also shows that the ideal of “solidarity” influenced both the preconditions for distinctions between public and private, and how views of businesses as illegitimate or legitimate actors in development aid activity changed over time.
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30.
  • Jensen, Kim Steen, et al. (author)
  • FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function
  • 2011
  • In: EMBO Journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 30:22, s. 4554-4570
  • Journal article (peer-reviewed)abstract
    • Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic tumour tissue in vivo and that FoxO3A shor-thairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia. The EMBO Journal (2011) 30, 4554-4570. doi:10.1038/emboj.2011.323; Published online 13 September 2011
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31.
  • Kadi, Fawzi, et al. (author)
  • The behaviour of satellite cells in response to exercise : what have we learned from human studies?
  • 2005
  • In: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 451:2, s. 319-327
  • Journal article (other academic/artistic)abstract
    • Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation of training is associated with a gradual reduction of the previously enhanced satellite cell pool. In the elderly, training counteracts the normal decline in satellite cell number seen with ageing. When the transcriptional activity of existing myonuclei reaches its maximum, daughter cells generated by satellite cell proliferation are involved in protein synthesis by enhancing the number of nuclear domains. Clearly, delineating the events and the mechanisms behind the activation of satellite cells both under physiological and pathological conditions in human skeletal muscles remains an important challenge.
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33.
  • Kjaer, Josefin, et al. (author)
  • Benefit of Primary Tumor Resection in Stage IV, Grade 1 and 2, Pancreatic Neuroendocrine Tumors : A Propensity-Score Matched Cohort Study
  • 2022
  • In: Annals of Surgery Open. - : Wolters Kluwer. - 2691-3593. ; 3:1
  • Journal article (peer-reviewed)abstract
    • Objective: To determine the association of primary tumor resection in stage IV pancreatic neuroendocrine tumors (Pan-NET) and survival in a propensity-score matched study.Background: Pan-NET are often diagnosed with stage IV disease. The oncologic benefit from primary tumor resection in this scenario is debated and previous studies show contradictory results.Methods: Patients from 3 tertiary referral centers from January 1, 1985, through December 31, 2019: Uppsala University Hospital (Uppsala, Sweden), Sahlgrenska University Hospital (Gothenburg, Sweden), and Brigham and Women’s Hospital/Dana-Farber Cancer Institute (Boston, USA) were assessed for eligibility. Patients with sporadic, grade 1 and 2, stage IV pan-NET, with baseline 2000–2019 were divided between those undergoing primary tumor resection combined with oncologic treatment (surgery group [SG]), and those who received oncologic treatment without primary tumor resection (non-SG). A propensity-score matching was performed to account for the variability in the extent of metastatic disease and comorbidity. Primary outcome was overall survival.Results: Patients with stage IV Pan-NET (n = 733) were assessed for eligibility, 194 were included. Patients were divided into a SG (n = 65) and a non-SG (n = 129). Two isonumerical groups with 50 patients in each group remained after propensity-score matching. The 5-year survival was 65.4% (95% CI, 51.5-79.3) in the matched SG and 47.8% (95% CI, 30.6-65.0) in the matched non-SG (log-rank, P = 0.043).Conclusions: Resection of the primary tumor in patients with stage IV Pan-NET and G1/G2 grade was associated with prolonged overall survival compared to nonoperative management. A surgically aggressive regime should be considered where resection is not contraindicated.
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34.
  • Kjaer, Josefin, et al. (author)
  • Long-term outcome after resection and thermal hepatic ablation of pancreatic neuroendocrine tumour liver metastases
  • 2021
  • In: BJS open. - : Oxford University Press (OUP). - 2474-9842. ; 5:4
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Pancreatic neuroendocrine tumours (Pan-NETs) are rare tumours that often present with or develop liver metastases. The aim of this retrospective study was to evaluate liver surgery and thermal hepatic ablation (THA) of Pan-NET liver metastases and to compare the outcomes with those of a control group. METHOD: Patients with Pan-NET treated in Uppsala University Hospital and Sahlgrenska University Hospital from 1995-2018 were included. Patient records were scrutinized for baseline parameters, survival, treatment and complications. RESULTS: Some 108 patients met the criteria for inclusion; 57 patients underwent treatment with liver surgery or THA and 51 constitute the control group. Median follow-up was 3.93years. Five-year survival in the liver surgery/THA group was 70.6 (95 per cent c.i. 0.57 to 0.84) per cent versus 42.4 (95 per cent c.i. 40.7 to 59.1) per cent in the control group (P=0.016) and median survival was 9.1 (95 per cent c.i. 6.5 to 11.7) versus 4.3 (95 per cent c.i. 3.4-5.2) years. In a multivariable analysis, surgery or THA was associated with a decreased death-years rate (hazard ratio 0.403 (95 per cent c.i. 0.208 to 0.782, P=0.007). CONCLUSION: Liver surgery and/or THA was associated with longer overall survival in Pan-NET with acceptable mortality and morbidity rates. These treatments should thus be considered in Pan-NET patients with reasonable tumour burden in an intent to alleviate symptoms and to improve survival.
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35.
  • Kjaer, Josefine, et al. (author)
  • Overall Survival in Patients with Stage IV Pan-NET Eligible for Liver Transplantation
  • 2023
  • In: World Journal of Surgery. - : Springer Nature. - 0364-2313 .- 1432-2323. ; 47, s. 340-347
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The use of liver transplantation (LT) in patients with stage IV neuroendocrine pancreatic tumors (pan-NET) is under debate. Previous studies report a 5-year survival of 27-53% after LT in pan-NET and up to 92.7% in patients with mixed NETs. This study aimed to determine survival rates of patients with stage IV pan-NET meeting criteria for LT while only subjected to multimodal treatment.METHODS: Medical records of patients with pan-NET diagnosed from 2000 to 2021 at a tertiary referral center were evaluated for eligibility. Patients without liver metastases, who did not undergo primary tumor surgery, age > 75 years and with grade 3 tumors were excluded. The patients were divided into groups; all included patients, patients meeting the Milan, the United Network for Organ Sharing (UNOS) or the European Neuroendocrine Tumor Society (ENETS) criteria for LT. Kaplan-Meier survival analysis was used to calculate overall survival.RESULTS: Out of 519 patients with pan-NET, 41 patients were included. Mean follow-up time was 5.4 years. Overall survival was 9.3 years (95% Cl 6.8-11.7), and 5-year survival was 64.7% (95% CI 48.2-81.2). Patients meeting the Milan, ENETS and UNOS criteria for LT had a 5-year survival of 64.9% (95% CI 32.2-97.6), 85.7% (95% CI 59.8-100.0) and 55.4% (95% CI 26.0-84.8), respectively.CONCLUSIONS: In patients with stage IV pan-NET, grade 1 and 2, with no extra abdominal disease, 5-year survival was 64.7% (95% CI 48.2-81.2). As these survival rates exceed previously published series of LT for pan-NET, the evidence base for this treatment is very weak.
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36.
  • Kjær, Kasper S., et al. (author)
  • Finding intersections between electronic excited state potential energy surfaces with simultaneous ultrafast X-ray scattering and spectroscopy
  • 2019
  • In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:22, s. 5749-5760
  • Journal article (peer-reviewed)abstract
    • Light-driven molecular reactions are dictated by the excited state potential energy landscape, depending critically on the location of conical intersections and intersystem crossing points between potential surfaces where non-adiabatic effects govern transition probabilities between distinct electronic states. While ultrafast studies have provided significant insight into electronic excited state reaction dynamics, experimental approaches for identifying and characterizing intersections and seams between electronic states remain highly system dependent. Here we show that for 3d transition metal systems simultaneously recorded X-ray diffuse scattering and X-ray emission spectroscopy at sub-70 femtosecond time-resolution provide a solid experimental foundation for determining the mechanistic details of excited state reactions. In modeling the mechanistic information retrieved from such experiments, it becomes possible to identify the dominant trajectory followed during the excited state cascade and to determine the relevant loci of intersections between states. We illustrate our approach by explicitly mapping parts of the potential energy landscape dictating the light driven low-to-high spin-state transition (spin crossover) of [Fe(2,2′-bipyridine)3]2+, where the strongly coupled nuclear and electronic dynamics have been a source of interest and controversy. We anticipate that simultaneous X-ray diffuse scattering and X-ray emission spectroscopy will provide a valuable approach for mapping the reactive trajectories of light-triggered molecular systems involving 3d transition metals.
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37.
  • Kjær, Kasper S., et al. (author)
  • Solvent control of charge transfer excited state relaxation pathways in [Fe(2,2′-bipyridine)(CN)4]2-
  • 2018
  • In: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 20:6, s. 4238-4249
  • Journal article (peer-reviewed)abstract
    • The excited state dynamics of solvated [Fe(bpy)(CN)4]2-, where bpy = 2,2′-bipyridine, show significant sensitivity to the solvent Lewis acidity. Using a combination of optical absorption and X-ray emission transient spectroscopies, we have previously shown that the metal to ligand charge transfer (MLCT) excited state of [Fe(bpy)(CN)4]2- has a 19 picosecond lifetime and no discernable contribution from metal centered (MC) states in weak Lewis acid solvents, such as dimethyl sulfoxide and acetonitrile.1,2 In the present work, we use the same combination of spectroscopic techniques to measure the MLCT excited state relaxation dynamics of [Fe(bpy)(CN)4]2- in water, a strong Lewis acid solvent. The charge-transfer excited state is now found to decay in less than 100 femtoseconds, forming a quasi-stable metal centered excited state with a 13 picosecond lifetime. We find that this MC excited state has triplet (3MC) character, unlike other reported six-coordinate Fe(ii)-centered coordination compounds, which form MC quintet (5MC) states. The solvent dependent changes in excited state non-radiative relaxation for [Fe(bpy)(CN)4]2- allows us to infer the influence of the solvent on the electronic structure of the complex. Furthermore, the robust characterization of the dynamics and optical spectral signatures of the isolated 3MC intermediate provides a strong foundation for identifying 3MC intermediates in the electronic excited state relaxation mechanisms of similar Fe-centered systems being developed for solar applications.
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41.
  • Larsson, Josefin, et al. (author)
  • The morphology of the ejecta in supernova 1987a : A study over time and wavelength
  • 2013
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 768:1, s. 89-
  • Journal article (peer-reviewed)abstract
    • We present a study of the morphology of the ejecta in Supernova 1987A based on images and spectra from the Hubble Space Telescope (HST) as well as integral field spectroscopy from VLT/SINFONI. The HST observations were obtained between 1994 and 2011 and primarily probe the outer H-rich zones of the ejecta. The SINFONI observations were obtained in 2005 and 2011 and instead probe the [Si I]+[Fe II] emission from the inner regions. We find a strong temporal evolution of the morphology in the HST images, from a roughly elliptical shape before similar to 5000 days, to a more irregular, edge-brightened morphology with a "hole" in the middle thereafter. This transition is a natural consequence of the change in the dominant energy source powering the ejecta, from radioactive decay before similar to 5000 days to X-ray input from the circumstellar interaction thereafter. The [Si I]+[Fe II] images display a more uniform morphology, which may be due to a remaining significant contribution from radioactivity in the inner ejecta and the higher abundance of these elements in the core. Both the Ha and the [Si I]+[Fe II] line profiles show that the ejecta are distributed fairly close to the plane of the inner circumstellar ring, which is assumed to define the rotational axis of the progenitor star. The Ha emission extends to higher velocities than [Si I]+[Fe II], as expected from theoretical models. There is no clear symmetry axis for all the emission. Instead, we find that the emission is concentrated to clumps and that the emission is distributed somewhat closer to the ring in the north than in the south. This north-south asymmetry may be partially explained by dust absorption. We compare our results with explosion models and find some qualitative agreement, but note that the observations show a higher degree of large-scale asymmetry.
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42.
  • Lohmander, Stefan, et al. (author)
  • Osteoarthritis
  • 2003
  • In: Textbook of sports medicine. - 0632065095 ; , s. 422-422:10, s. 1402-1430, s. 1301-1301
  • Book chapter (other academic/artistic)
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43.
  • Mackey, Abigail L., et al. (author)
  • Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication
  • 2016
  • In: The FASEB Journal. - Bethesda, USA : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 30:6, s. 2266-2281
  • Journal article (peer-reviewed)abstract
    • With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1(+) satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7(+) cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.
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44.
  • Magnusson, S. Peter, et al. (author)
  • Heterotopic Ossification After an Achilles Tendon Rupture Cannot Be Prevented by Early Functional Rehabilitation: A Cohort Study
  • 2020
  • In: Clinical Orthopaedics and Related Research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-921X .- 1528-1132. ; 478:5, s. 1101-1108
  • Journal article (peer-reviewed)abstract
    • Background Tendon loading might play a role in the development of heterotopic ossification after Achilles tendon ruptures. Early heavy loading on a healing tendon in animals has been shown to prolong the proinflammatory response, and inflammatory cells are thought to drive heterotopic ossification formation. Taken together, this suggests that early rehabilitation might influence heterotopic ossification development. Questions/purposes The purposes of this study were to investigate (1) whether the presence of heterotopic ossification after Achilles tendon ruptures influences clinical outcome and (2) whether early mobilization or weightbearing prevents the development of heterotopic ossification. Methods This was a retrospective analysis of 69 patients from a previous clinical trial. All patients were treated surgically, but with three different early rehabilitation protocols after surgery: late weightbearing and ankle immobilization, late weightbearing and ankle mobilization, and early weightbearing and ankle mobilization. Plain radiographs taken 2, 6, 12, 26, and 52 weeks postoperatively were analyzed for heterotopic ossification, which was detected in 19% of patients (13 of 69) at 52 weeks. Heterotopic ossification was measured, scored, and correlated to clinical outcomes; heel-raise index (HRI), ankle joint ROM, tendon strain, Achilles tendon rupture score (ATRS), and Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire scores at 26 and 52 weeks postoperatively. Results Heterotopic ossification had no adverse effects on patient-reported outcomes (ATRS or VISA-A), tendon strain, or ROM. In fact, patients with heterotopic ossification tended to have a better HRI at 52 weeks compared with patients without (mean difference 14% [95% CI -0.2 to 27]; p = 0.053). Neither the occurrence (heterotopic ossification/no heterotopic ossification) nor the heterotopic ossification severity (ossification score) differed between the three rehabilitation groups. Seventeen percent of the patients (four of 24) with early functional rehabilitation (early weightbearing and ankle joint mobilization exercise) had heterotopic ossification (score, 2-3) while late weightbearing and immobilization resulted in heterotopic ossification in 13% of the patients (score, 3-4). Conclusions Heterotopic ossification occurs relatively frequently after Achilles tendon ruptures but appears to have no adverse effects on functional outcomes. Furthermore, heterotopic ossification develops during the first 6 weeks after rupture, and weightbearing or ankle-joint mobilization does not prevent this from occurring.
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45.
  • Marouli, Eirini, et al. (author)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Journal article (peer-reviewed)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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46.
  • Pallas, Josef, 1974- (author)
  • Talking Organizations : Corporate Media Work and Negotiations of Local Practice
  • 2007
  • Doctoral thesis (other academic/artistic)abstract
    • Contemporary business organizations are becoming increasingly medialized. The present thesis builds on the assumption that the media play an important part in shaping relations between organizations and their environments, and that we need to know more about the way organizations respond to and influence the media and the production of news. Following a close examination of thirteen major Swedish corporations and their media activities it has been suggested that business organizations are actively involved not only in direct media work, i.e. activities concerned with news coverage, but also in influencing the organizational and professional settings in which the production of news occurs. This involvement on the part of the companies embraced the production of media texts, the development of various relationships with the media, organizational arrangements for their Corporate Communications departments, and the professionalization of company-media interaction.This corporate involvement has been perceived as being exercised via a set of purposeful negotiations whereby the companies contribute to the co-shaping of the short-term conditions for the coverage of news regarding their conduct, as well as other general settings consisting the routines, norms and expectations that shape their long-term interactions with the media. It has been concluded that more attention should be paid to company-media activities identified as a negotiated local practice. This practice constitutes a formal behavioural frame of reference for the interacting actors, as it allows for the possibility of mutual adjustments and professional improvisations. Thus, with its suggestion for bridging between institutional expectations and locally developed solutions, the notion of negotiated local practices gives us a more comprehensive understanding of the way individual organizations interact with and co-shape their environments.
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47.
  • Schaltz-Buchholzer, Frederik, et al. (author)
  • BCG skin reactions by 2 months of age are associated with better survival in infancy : A prospective observational study from Guinea-Bissau
  • 2020
  • In: BMJ Global Health. - : BMJ. - 2059-7908. ; 5:9
  • Journal article (peer-reviewed)abstract
    • Introduction Receiving Bacille Calmette-Guérin (BCG)-Denmark vaccine at birth has been associated with ∼40% reductions in all-cause neonatal mortality. We evaluated determinants of BCG skin reaction characteristics by age 2 months and tested the association with subsequent mortality. Methods Prospective observational study amalgamating five trials providing BCG-at-birth that were conducted between 2002 and 2018 in Guinea-Bissau. The reaction status and size were evaluated at home-visits by 2 months of age among 6012 neonates; mortality from 2 to 12 months was assessed at subsequent visits. Reaction determinants were evaluated by binomial regression providing risk ratios (RRs). In Cox-models providing adjusted mortality rate ratios (aMRRs), we assessed the association between (1) having a 2-month reaction (yes/no) and (2) reaction size tertiles and subsequent all-cause mortality risk. A subgroup had their BCG reaction evaluated and were bled at age 4 weeks; their samples underwent in vitro analysis for specific and non-specific cytokine responses. Results The BCG strain was the main determinant for developing a 2-month reaction and the reaction size: the BCG-Russia/BCG-Denmark RR for large-reaction was 0.38 (0.30-0.47) and the BCG-Russia/BCG-Japan RR was 0.61 (0.51-0.72). 5804 infants (96.5%) were reactors by age 2 months; 208 (3.5%) were non-reactors. The 2-12 months mortality risk was 4.8% (10/208) for non-reactors, 2.9% (64/2213) for small reactors, 1.8% (30/1710) for medium reactors and 0.8% (15/1881) for large reactors. The reactor/non-reactor aMRR was 0.49 (0.26-0.95) and there was a linear trend of decreasing mortality with increasing reaction size (p for trend <0.001). BCG reactors had higher 4-week specific and non-specific cytokine responses, responses that were highest among those with large reactions. Conclusion Among BCG-vaccinated infants, having a BCG skin reaction by age 2 months was associated with markedly better survival, as was the reaction size. Our findings thus support that BCG has substantial effects on all-cause mortality. Emphasising at-birth vaccination with immunogenic BCG strains and revaccinating non-reactors and small reactors could have major public health benefits.
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50.
  • Tatsuno, Hideyuki, et al. (author)
  • Hot Branching Dynamics in a Light-Harvesting Iron Carbene Complex Revealed by Ultrafast X-ray Emission Spectroscopy
  • 2020
  • In: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:1, s. 364-372
  • Journal article (peer-reviewed)abstract
    • Iron N-heterocyclic carbene (NHC) complexes have received a great deal of attention recently because of their growing potential as light sensitizers or photocatalysts. We present a sub-ps X-ray spectroscopy study of an FeIINHC complex that identifies and quantifies the states involved in the deactivation cascade after light absorption. Excited molecules relax back to the ground state along two pathways: After population of a hot 3MLCT state, from the initially excited 1MLCT state, 30 % of the molecules undergo ultrafast (150 fs) relaxation to the 3MC state, in competition with vibrational relaxation and cooling to the relaxed 3MLCT state. The relaxed 3MLCT state then decays much more slowly (7.6 ps) to the 3MC state. The 3MC state is rapidly (2.2 ps) deactivated to the ground state. The 5MC state is not involved in the deactivation pathway. The ultrafast partial deactivation of the 3MLCT state constitutes a loss channel from the point of view of photochemical efficiency and highlights the necessity to screen transition-metal complexes for similar ultrafast decays to optimize photochemical performance.
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